Corticoterapia
Corticotherapy
Hisbello S. Campos
Resumo
Glicocorticosteroides são fármacos efetivos no tratamento de doenças inflamatórias e imunes. Agem em praticamente todas as células do corpo, antagonizando os efeitos patogênicos de inúmeras doenças. A maior parte de seus efeitos parece ser produto de sua ligação a receptores específicos armazenados no interior das células. Suas ações moduladoras da transcrição genética iniciam-se com a ligação ao seu receptor e posterior conexão aos genes alvo, num processo que conta com a participação de outros fatores e envolve múltiplos mecanismos (ação genômica). Os genes alvo incluem aqueles responsáveis por mediadores inflamatórios, como quimiocinas, citocinas, fatores de crescimento e seus receptores. Além de seus efeitos sobre o DNA, estimulando a produção de produtos anti-inflamatórios ou inibindo a transcrição de genes pró-inflamatórios, via acetilação ou deacetilação das histonas, respectivamente, os glicocorticosteroides possuem outros mecanismos de ação que não envolvem regulação genética (ação não genômica). Aparentemente, por mecanismos ainda não esclarecidos, os efeitos da corticoterapia são produto da associação das ações genômicas com as não genômicas. Os glicocorticosteroides representam o grande pilar terapêutico da asma, com efeitos sobre as células estruturais e funcionais do trato respiratório. Nessa situação particular, na qual costumam ser empregados continuadamente por períodos prolongados, com risco potencial de efeitos indesejáveis relevantes, é fundamental desvendar os processos envolvidos em seus mecanismos de ação para tentar desenvolver meios de reduzir os riscos associados e potencializar os efeitos desejados.
Palavras-chave
Abstract
Glucocorticosteroids are effective drugs in the treatment of inflammatory and immune diseases. They act on virtually every cell in the body by antagonizing the pathogenic effects of numerous diseases. Most of its effects appear to be the product of its binding to specific receptors stored within cells. Its modulatory actions on genetic transcription begin with a linkage to its receptor and later connection to target genes, in a process that counts on the participation of other factors and involves multiple mechanisms (genomic action). Target genes include those responsible for inflammatory mediators, such as chemokines, cytokines, growth factors, and their receptors. In addition to its effects on DNA, stimulating the production of anti-inflammatory products or inhibiting the transcription of pro-inflammatory genes, via acetylation or deacetylation of histones, respectively, glucocorticosteroids have other mechanisms of action that do not involve genetic regulation (non-genomic effect). Apparently, by mechanisms not yet clarified, the effects of corticotherapy are the product of the association of genomic and non-genomic actions. Glucocorticosteroids represent the great therapeutic pillar of asthma, with effects on structural and functional cells of the respiratory tract. In this particular situation, where they are often used for prolonged periods, with a potential risk of relevant undesirable effects, it is essential to uncover the processes involved in their mechanisms of action in order to develop ways to reduce the associated risks and potentiate the desired effects
Keywords
Referências
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Submetido em:
22/06/2018
Aceito em:
30/08/2018
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